Until recently, the human immune system was often thwarted by cancer cells and their ability to grow and spread seemingly unchecked.
But in the last two decades, inroads made in immunotherapy—treatments designed to harness a patient’s own immune system to unmask and destroy these deadly cancer cells—have led to some remarkable successes. Already, some patients with melanoma, non-small cell lung cancer, bladder cancer, kidney cancer, stomach cancer, liver cancer, head and neck cancers, and lymphoma are seeing its benefits, and the approach is showing promise in small cell lung cancer and ovarian cancer.
Challenges Faced by Immunotherapy
So far, most cancer patients, especially those with pancreatic cancer, don’t see any benefit. The reasons are numerous.
For example, one of the challenges to pancreatic cancer immunotherapy approaches has been the tumor’s ability to evade the immune response. Specifically, pancreatic tumors can prevent the recruitment of T cells, immune cells that could otherwise recognize and attack the cancer cells as foreign. Early detection of the disease has also been difficult, and currently there is still a less than optimal response to standard treatments. KRAS, one of the primary mutations found in pancreatic cancer, is considered “undruggable,” a term used to describe proteins that can’t be targeted with drugs, though significant research is underway to meet this challenge.
However, there have been recent events that have brightened the prospect of immunotherapy for pancreatic cancer. In a first-of-its-kind of decision earlier this year, the U.S. FDA approved Keytruda for the treatment of solid tumors exhibiting high microsatellite instability mismatch-repair deficiency. Although only about 3 to 4 percent of pancreatic cancer patients fit this profile, it can be a potential game-changer for them, explains Luis A. Diaz, M.D., Head of the Division of Solid Tumor Oncology in the Department of Medicine at Memorial Sloan Kettering Cancer Center in New York.
However, “more than 95 percent of pancreas cancer patients still are unable to take advantage of immunotherapy,” he says. “Immunotherapy as we know it today has not made a lot of advances or had a lot of success for them. We absolutely need to get a better handle on the biology of the disease, especially the surrounding tumor stroma. Once we understand more, immunotherapy trials may show better results.”
Although pancreas cancer does indeed present numerous challenges, Diaz is adamant that “no one is giving up, and we can build upon some prior success.” He adds, “But we need to get a lot more creative and not simply repeat mistakes. Because that is what will ultimately benefit our patients.”
Many Clinical Trials
Indeed, there are numerous trials underway exploring the use of novel antibodies that cut the brakes on the immune system, as well as vaccine approaches and genetically reprogramming immune cells so they can fight cancer, among other efforts.
Diaz emphasized that patients who are newly diagnosed with pancreatic cancer should always be considered for clinical trials. “There are clinical trials in different classes of agents, and also, patients who are now being referred for immunotherapy trials,” he says, although at this time there is not a standard treatment immunotherapy.
“It would be arrogant to say that immunotherapy won’t work in pancreatic cancer because the truth is we don’t know,” Diaz adds. “What I do know is there is an active effort to really understand the immunotherapy problem in this disease and to try to put a treatment strategy in place.”
An Immunotherapy Primer
For pancreatic cancer, immunotherapy approaches generally fall into four main categories; checkpoint inhibitors, therapeutic vaccines, adoptive T cell transfer, and monoclonal antibodies.
- Checkpoint Inhibitors: Checkpoint inhibitors are a type of drug that blocks certain proteins made by some types of immune system cells, such as T cells, and some cancer cells that keep immune responses in check. When these proteins are blocked or inhibited, T cells are better able to kill cancer cells.
- Vaccines: Unlike a flu or measles vaccine to help prevent illness, cancer treatment vaccines attack a disease that is already present. Vaccines vary with some comprised of cancer cells, parts of cells, or pure antigens. In some instances, a patient’s own immune cells are used to create the vaccine.
- Adoptive T Cell Transfer: This technique involves collecting and using patients’ own immune cells to treat their cancer. This approach has been tested in a number of clinical trials, resulting in significant responses for patients with advanced blood cancers. Trials are underway for solid tumors, such as pancreatic cancer.
- Monoclonal Antibodies: One form of immune therapy uses injections of man-made monoclonal antibodies to home in on a specific molecule, such as carcinoembryonic antigen (CEA), while leaving normal cells alone.